Evaluation of Finerenone, Dapagliflozin, and Ambrisentan in Biomarker-Guided Treatment of Chronic Kidney Disease-Associated Albuminuria
- Trial ID
- 2023-507449-27-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical validation study is to evaluate the effect of a **biomarker** response-guided treatment approach compared to guideline care on **albuminuria** in patients with chronic kidney disease. This is clinically relevant as albuminuria is a key indicator of kidney damage and its reduction is associated with improved renal outcomes.
Secondary objectives include:
- Comparing the effect of a biomarker response-guided treatment approach versus guideline care on estimated glomerular filtration rate (**eGFR**), a surrogate endpoint for long-term kidney failure.
- Establishing a communication framework to educate study participants about their drug response and therapy decisions. This involves developing effective communication tools to inform participants and investigators about treatment decisions based on integrated biomarker responses, with input from health counselors, nephrologists, and a patient advisory panel.
- Comparing the effect of a biomarker response-guided treatment approach versus guideline care on the **KidneyIntelX** score, a surrogate endpoint for treatment response.
Participants
The clinical trial involves a total of **10 participants** diagnosed with **chronic kidney disease**. The study population includes both male and female subjects, aged between 18 and 75 years. Participants were selected based on specific criteria, including an estimated glomerular filtration rate (eGFR) of at least 25 mL/min/1.73m² and a urine albumin-to-creatinine ratio (UACR) greater than 100 mg/g in two consecutive first-morning void urine samples. Individuals with a UACR between 80-100 mg/g were considered if historical measurements exceeded 100 mg/g and could not be attributed to new treatments. All participants are required to be on a maximum tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for a minimum of four weeks prior to enrollment. The trial does not include a vulnerable population, and participants must be able to communicate effectively with the study staff and provide informed consent. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of a **biomarker** response-guided treatment approach compared to standard guideline care in patients with **chronic kidney disease**. This study is a randomized, open-label, controlled trial with a primary focus on the change in albuminuria from baseline to week 36. The trial will involve the administration of **finerenone**, **dapagliflozin**, and **ambrisentan**, all administered orally, with a maximum treatment period of 64 weeks. The trial is expected to commence recruitment on June 1, 2024, and conclude by June 30, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (18-75 years), estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR). Eligible participants must have been on a stable dose of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for at least four weeks prior to enrollment. Following randomization, participants will attend follow-up visits at specified intervals to monitor treatment effects and safety, with the primary endpoint assessed at week 36. Secondary endpoints include changes in eGFR and KidneyIntelX score, with assessments extending to week 64 and week 66.
The expected duration of participant involvement is approximately 66 weeks, encompassing the treatment and follow-up phases. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or non-compliance with study protocols. The trial aims to develop a communication tool by the end of the study to guide patients and healthcare professionals in utilizing biomarker-guided treatment effectively.
Treatment
The clinical trial involves the administration of **FINERENONE**, a chemical compound with the synonym BAY 94-8862. It is classified under the ATC code C03DA05. The pharmaceutical form of FINERENONE is denoted as PHF00082MIG, and it is administered orally. The maximum daily dose is 10 mg, with a total maximum dose of 10 mg over a treatment period of 64 days. The administration schedule is designed to ensure participant compliance, with regular monitoring to assess adherence to the dosing regimen.
**DAPAGLIFLOZIN** is another experimental medication used in this study. It is also administered in the pharmaceutical form PHF00082MIG and taken orally. The maximum daily and total dose for DAPAGLIFLOZIN is 10 mg, consistent with a treatment duration of 64 days. As with FINERENONE, participant compliance is monitored to ensure adherence to the prescribed dosing schedule.
The study also includes the use of **AMBRISENTAN**, which is provided in a film-coated tablet form. The active substance, AMBRISENTAN, is administered orally with a maximum daily and total dose of 2.5 mg over the same 64-day treatment period. The administration of AMBRISENTAN involves a dose reduction and encapsulation process, and participant compliance is closely monitored to ensure proper adherence to the treatment protocol.
All medications in this trial are administered orally, and the study design includes mechanisms to monitor and ensure participant compliance with the dosing schedules. The trial does not involve any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. The focus is on evaluating the effects of these experimental medications on the study's primary objective.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint involves a between-group comparison of the change in albuminuria, specifically the urinary albumin-to-creatinine ratio (UACR), from baseline (randomization) to week 36. This measurement will provide insight into the effect of the treatment on albuminuria levels over the specified period.
Secondary endpoints include several between-group comparisons: the change in estimated glomerular filtration rate (**eGFR**) from week 16 to week 64, from baseline to week 64, and from baseline to week 66. Additionally, the change in KidneyIntelX score from baseline to week 36 will be evaluated. These endpoints will help determine the impact of the treatment on kidney function and risk stratification over time.
The trial will also aim to develop a communication tool by the end of the study to instruct patients and healthcare professionals on using biomarker-guided treatment. Efficacy parameters will be collected and analyzed at specified timepoints, ensuring a comprehensive evaluation of the treatment's impact on chronic kidney disease.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 18 and ≤ 75 years
- eGFR ≥ 25 mL/min/1.73m2
- UACR > 100 mg/g (10 mg/mmol) in two consecutive first-morning void urine samples. UACR 80-100 mg/g is accepted if historical measurements are above 100 mg/g and if it cannot be explained by any new treatment.
- Participants must be on a maximum tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for at least four weeks before enrollment.
- Ability to communicate with the study staff and understand and sign the informed consent.
Exclusion Criteria
- Age < 18 years or > 75 years
- Eligible to receive at least two of three study treatments. Participants meeting two or more of the following criteria will be excluded: a. Potassium > 5.0 mmol/L b. Heart failure NYHA class III or IV or NT-proBNP > 600 pg/ml c. Not a candidate for treatment with an SGLT2 inhibitor, e.g., due to contraindications (according to the Forxiga SmPC) or previously experienced side effects from an SGLT2 inhibitor.
- NT-proBNP > 1200 pg/ml
- Severe peripheral or facial edema (according to the investigator's opinion)
- Diagnosis of unstable angina pectoris and/or myocardial infarction within the last six months.
- Already receiving treatment with two of the three study drugs (for example, an SGLT2 inhibitor and finerenone).
- Treatment with a potassium-sparing diuretic or a mineralocorticoid receptor antagonist, except for finerenone (e.g., spironolactone, eplerenone, or amiloride)
- Elevated Alanine Aminotransferase (ALT) > 3 x upper normal limit, autoimmune hepatitis, and/or severe hepatic impairment (including but not limited to a history of hepatic encephalopathy, a history of esophageal varices or a history of portocaval shunt.)
- Autosomal dominant or autosomal recessive polycystic kidney disease
- Lupus nephritis or ANCA-associated vasculitis, or any other primary or secondary kidney disease requiring immunosuppressive therapy within 6 months prior to screening
- Kidney transplant
- Dialysis
- Addison's disease
- Concomitant treatment with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, cobicistat, clarithromycin)
- Idiopathic pulmonary fibrosis
- Type 1 diabetes
- Known or suspected hypersensitivity to the study medications or related products
- Presence or history of malignant neoplasms (except basal cell skin cancer or squamous cell skin cancer) within 5 years before screening.
- Any other history, condition, therapy, or uncontrolled intercurrent illness that could, as judged by the investigator, affect participant safety or compliance with study requirements.
- A female who is pregnant, breastfeeding, or intends to become pregnant, or women of childbearing potential (WOCBP) who are not using highly effective contraceptive methods.
- A female who is pregnant, breastfeeding, or intends to become pregnant, or women of childbearing potential (WOCBP) who are not using highly effective contraceptive methods.
- Participant in another intervention study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Not Yet Recruiting | 01 Jun 2024 | 40 |
 Germany | Not Yet Recruiting | 01 Jun 2024 | 10 |
 Italy | Not Yet Recruiting | 01 Jun 2024 | 45 |
 Spain | Not Yet Recruiting | 01 Jun 2024 | 15 |
 Sweden | Not Yet Recruiting | 01 Jun 2024 | 5 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
FINERENONE | Test | PHF00082MIG | ORAL | 10 | 64 | SCP54959918 |
DAPAGLIFLOZIN | Test | PHF00082MIG | ORAL | 10 | 64 | SCP153584 |
AMBRISENTAN | Test | — | ORAL USE | 2.5 | 64 | SUB25424 |